Field of the Invention
The present invention relates to a manufacturing method of two-chamber type combined container-syringe.
Priority is claimed on Japanese Patent Application No. 2013-098825, filed on May 8, 2013, the content of which is incorporated herein by reference.
Description of Related Art
A combined container-syringe where a syringe is internally filled with an injection preparation and which is designed so that immediate injection for a patient is allowed by being unpacked from a packaging material when in use has been widely adopted by medical institutions around the world, from the viewpoint of convenience, safety and preventing injection drugs from being misused.
In recent years, a so-called two-chamber type combined container-syringe has been introduced in which a front chamber of one syringe is filled with a powder preparation or a lyophilized preparation and a rear chamber is filled with a dissolving solution, a dispersion medium or a suspending solution, and an injection drug is prepared by dissolving or suspending both of these when in use. Among various types of the two-chamber type combined container-syringe, the type disclosed in Japanese Patent No. 1759157 has been known as the most widely adopted.
In the two-chamber type combined container-syringe, a plastic front assembly is fitted to a distal end portion of a glass cartridge, and a finger grip for finger hooking is fitted to a rear end portion. In addition, a bypass which allows the front chamber and the rear chamber to communicate with each other is molded in an approximately central portion of the cartridge having a cylindrical shape. The powder preparation or the lyophilized preparation filled in the inside of the front chamber is sealed in air-tight and liquid-tight manners by a front stopper and a middle stopper, and in addition, the dissolving solution to solve or to suspend the powder preparation or the lyophilized preparation filled in the inside of the rear chamber is sealed in the air-tight and liquid-tight manners by the middle stopper and an end stopper, respectively.
When injection is performed, the end stopper moves forward by pushing a plunger rod, which screws a female screw provided in a rear portion of the end stopper to a male screw in a distal end, toward the front of the syringe. Accordingly, the middle stopper inserted in the anterior end of the rear chamber moves forward together with the dissolving solution filled inside the rear chamber. When the middle stopper reaches a bypass portion molded in a cartridge, the seal is released by the bypass, and thus the dissolving solution flows into the front chamber through the bypass. At a stage when the entire solution in the rear chamber flows into the front chamber and when the distal end of the middle stopper is further pushed by the end stopper passes through the bypass portion, the pushing of the plunger rod is stopped. By properly shaking the entire syringe and by sufficiently dissolving (suspending) the powder preparation and the lyophilized preparation with the dissolving solution, the injection drug is prepared. By pushing the plunger rod, the front stopper is inserted into a bypass chamber provided in the inner portion of a hub luer-lock. By a longitudinal groove on an inner wall of the bypass chamber, a medicinal solution inside the syringe is introduced into an injection needle from an outlet hole of a cylindrical tip. Then, air bubbles remaining inside the front chamber are discharged by further pushing the plunger rod, and thus the injection drug is introduced to the injection needle through the cylindrical tip of the hub luer-lock and injected to a patient.
In this type of the two-chamber type combined container-syringe, a solution, such as the dissolving solution is filled and sealed in the rear chamber, in a state where a glass cartridge is a single body before fitting the front assembly and the finger grip to both ends of the glass cartridge and steam sterilization is performed, and then the lyophilization solution is filled and lyophilized or powder preparation is filled and sealed in the front chamber, and after that, the front assembly or the finger grip can be aseptically fitted. For this reason, the use of this type of two-chamber type combined container-syringe as a combined container-syringe for various kinds of injection drug has been planned and developed.
Technology disclosed in Japanese Patent No. 5081330 and Japanese Patent No. 4638553 have been known as a method of filling and sealing the glass cartridge of this type of two-chamber type combined container-syringe with the medicinal solution. In the disclosed technology, after attaching a plastic holder to the single body of the glass cartridge of the above-described two-chamber type combined container-syringe and putting a plurality of the glass cartridges attached with plastic holders to a plastic nest, it is possible to sterilize by putting the entire body into a tub (container) and covering an upper surface of the tub with a non-woven fabric or a synthetic paper that is sterilizable and by heat sealing the periphery thereof. In this manner, it is possible to attach the holder to the glass cartridge which is washed in advance, and of which an inner surface is coated by a lubricant such as silicone oil and dried, to insert the plurality of the glass cartridges to through-holes of the nest, to put into the tub whose upper surface is heat sealed with the non-woven fabric or the synthetic paper, and to sterilize with high pressure steam or ethylene oxide gas (EOG).
According to such technologies disclosed in Japanese Patent No. 5081330 and Japanese Patent No. 4638553, first, the packaged and sterilized glass cartridges which are put into the tub are set in filling equipment together with the tub, a lid member that seals an upper end of an opening portion of the tub is mechanically detached within the equipment, and the glass cartridges in the nest are unpacked from the tub together with the nest. Then, a filling process is performed in which the end stopper is inserted into the glass cartridge supported by the holder and the nest from an upper part thereof, the middle stopper is inserted after filling the glass cartridge with the dissolving solution, and the dissolving solution is sealed inside the glass cartridge. Then, the steam sterilization is performed while the glass cartridge is filled with the dissolving solution.
The filling process is performed in which each glass cartridge is filled with a main preparation lyophilized from the upper part of each glass cartridge by the same type of the filling equipment, the front stopper is inserted on the sterilized dissolving solution, and thus the main preparation is sealed inside the glass cartridge. Then, the glass cartridge filled with the main preparation is loaded and the lyophilization is performed in a freeze dryer while the glass cartridge filled with the main preparation is inserted in the nest. And then, a process of pushing the front stopper that has been raised in a half-plugged state from the inside of the glass cartridge into the glass cartridge is performed by lowering a shelf plate in the freeze dryer.
According to such a manufacturing method of two-chamber type combined container-syringe, the glass cartridge is in a state of being horizontally movable together with the holder in a range of the internal diameter of the through-hole of the nest. For this reason, there are advantages that it is easy to position the glass cartridge and it is possible to perform a plurality of filling the dissolving solution operations by one line along the alignment of the through-holes of the nest at a time. In other words, it is possible to perform a process from filling the glass cartridge with the dissolving solution to completing the lyophilization in one nest without the glass cartridge as a main member being removed or transferred.